Abstract

Background: Although the SARS-CoV2 mRNA vaccines have proven high efficacy in clinical trials, there is limited data on the impact of age, sex, and side effects on vaccine-induced immune responses.Methods: We studied the development of SARS-CoV-2 S-RBD antibodies after the Comirnaty mRNA vaccine in 118 healthy volunteers and correlated immune response with age, sex, and side effects of the vaccinations.Findings: We show a robust immune response to the S-RBD region after the first and the second vaccination dose. We saw a decline of antibody levels at 6 weeks versus 1 week after the second dose, suggesting a waning of the immune response over time. Regardless of this, the antibody levels at 6 weeks after the second dose remained significantly higher than before the vaccination, after the first dose, or in COVID-19 convalescent individuals. We found a decreased vaccination efficacy but fewer adverse events in older individuals, and that vaccination is less efficient in older males whereas the detrimental impact of age on vaccination outcome is abolished in females at 6 weeks after the second dose.Interpretation: The vaccine induces a strong immune response but older individuals develop fewer side effects and decreased antibody levels at 6 weeks. The waning of antibodies in particular in older male individuals suggests that both age and male sex act as risk factors in the immune response to the vaccine.Funding: The study was supported by the Centre of Excellence in Translational Genomics (EXCEGEN), the Estonian Research Council grant PRG377 and SYNLAB Estonia.Declaration of Interests: None to declare.Ethics Approval Statement: The study has been approved by the Research Ethics Committee of the University of Tartu on February 15, 2021 (nr 335/T-21).

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